Fx-5A Safety and Tolerability in Healthy Volunteers

Overseen By Marcelo J Amar, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Must not be taking: Supplements, Medications

Disqualifiers: Pregnancy, Hypertension, Obesity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 39

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of a new drug called Fx-5A, a peptide-lipid complex that could potentially treat heart disease and inflammation. Researchers will examine the drug's effects on healthy individuals to ensure safety before further testing. The trial requires a hospital stay of 36-48 hours for monitoring, including blood tests and heart monitoring. Healthy individuals who do not take medications or supplements and have no known allergies to the drug might be suitable candidates. Participants will attend follow-up visits after their hospital stay to monitor any effects. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects on people.

Will I have to stop taking my current medications?

Yes, participants must stop taking any supplements or medications for at least 8 weeks before joining the trial, except for oral contraceptives.

Is there any evidence suggesting that Fx-5A is likely to be safe for humans?

Research has shown that Fx-5A is generally well-tolerated. In animal studies, particularly with non-human primates (NHPs), Fx-5A did not cause harm even at the highest dose tested, 75 mg per kilogram per day, suggesting safety at those levels.

While these results are encouraging, it is important to remember that this is an early-stage study in humans. Early phase trials aim to determine the safety and tolerability of a treatment for people. Unknowns may still exist regarding how Fx-5A will affect humans. Researchers closely monitor trial participants to address any potential side effects promptly. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Fx-5A is unique because it targets a new mechanism by acting on specific pathways involved in inflammation and lipid metabolism. Unlike traditional treatments that may focus on symptoms or general inflammation, Fx-5A aims to address the root causes at a molecular level. This targeted approach could lead to more effective management with potentially fewer side effects, which is why researchers are excited about its potential.

What evidence suggests that Fx-5A might be an effective treatment for cardiovascular diseases?

Research has shown that Fx-5A, the investigational treatment in this trial, may help reduce atherosclerosis, a condition where arteries become clogged with fatty deposits. In studies with rabbits and mice, Fx-5A slowed the development of this condition. The drug imitates parts of good cholesterol (HDL) to help remove bad cholesterol (LDL) and decrease inflammation. It targets a specific part of cells that prevents artery clogging. These findings suggest that Fx-5A could help manage heart disease and inflammation by addressing these underlying issues. ^{2 3 5 6 7}

Who Is on the Research Team?

Marcelo J Amar, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

Healthy adults over 18, not pregnant, willing to use birth control and avoid other studies. Excludes those with allergies to Fx-5A components, recent blood donors, kidney or liver issues, uncontrolled hypertension, recent investigational drug use or certain medication/supplement intake.

Inclusion Criteria

I am willing and able to sign a consent form.

Women of childbearing potential must be willing to use an appropriate form of birth control during the course of the study and two forms of birth control during the interventional portion of the study and up to day 7 after infusion

Subject willing to return for all study visits, complete all study-related tasks, and agree not to participate in other research studies from screening visit to study completion

Exclusion Criteria

Subjects may also be excluded for any reason that may compromise their safety or the accuracy of research data collection.

I have been taking supplements or medications for at least 8 weeks, except for birth control pills.

Blood donation equal to or above 500 mL within 2 months prior to dosing

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

0-4 weeks

1 visit (in-person)

Intervention

Participants receive a single intravenous infusion of Fx-5A and are monitored for 24 hours

2 days

Inpatient stay for 36-48 hours

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits on day 7 and day 28

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Fx-5A

Trial Overview The trial tests the safety and effects of a new heart disease treatment called Fx-5A in healthy volunteers. It involves a hospital stay for monitoring via EKGs and blood tests after receiving an infusion of Fx-5A.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 1 Intervention

subjects entered into the trial may go thru a 0-4 weeks screening (Screening Phase). On the Intervention phase, subjects will be followed for 7 days which includes: entry criteria assessments and settling at the inpatient unit on Day 0, a single-dose I.V. infusion with data collection on Day 1 followed by 24 hours monitoring (Day 2), a 7-day and 28-day outpatient follow-up visit (Follow-Up Phase).

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The novel Liposome Aggregate Platform (LAP) system significantly enhances the retention of Flurbiprofen (FLB) in ocular tissues after intravitreal injection, compared to traditional liposomes, suggesting improved efficacy for treating posterior eye conditions.

The LAP system also reduces inflammation associated with certain dyes, indicating a potential safety advantage, while demonstrating prolonged drug release and retention, making it a promising approach for ocular therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Liposome Aggregate Platform (LAP) system for sustained retention of drugs in the posterior ocular segment following intravitreal injection. Blazaki, S., Pachis, K., Tzatzarakis, M., et al.[2020]

The synthesized prodrugs of 5-fluoro-2'-deoxyuridine, when incorporated into liposomes, showed 10 to 30 times greater activity against murine colon cancer compared to the free drug, indicating enhanced efficacy as a cancer treatment.

However, the prodrug-liposome preparations were found to be 20-60 times more toxic than the parent drug, highlighting a need for careful consideration of safety in their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

5'-O-Palmitoyl- and 3',5'-O-dipalmitoyl-5-fluoro-2'-deoxyuridine--novel lipophilic analogues of 5'-fluoro-2'-deoxyuridine: synthesis, incorporation into liposomes and preliminary biological results. Schwendener, RA., Supersaxo, A., Rubas, W., et al.[2019]

In a pilot study involving patients with fulminant hepatic failure, those treated with polyunsaturated phosphatidyl choline (PPC) showed a faster recovery from encephalopathy and a lower mortality rate compared to the control group.

Patients with subacute hepatic failure also benefited from PPC treatment, experiencing quicker recovery from encephalopathy, lower mortality rates, and significantly higher regression of ascites, indicating its potential efficacy in liver failure conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of polyunsaturated phosphatidyl choline in fulminant and subacute hepatic failure. Singh, NK., Prasad, RC.[2006]

The study developed two novel steroid-modified ether phospholipids that are structurally similar to a newly identified hydroxy-PAF analogue, which may have therapeutic potential due to their ability to modulate inflammation.

These new compounds were found to effectively antagonize the activity of platelet activating factor (PAF), showing reduced platelet aggregation, which suggests they could be useful in treating conditions related to excessive inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of novel steroid-modified ether phospholipids. Karantonis, HC., Pitsinos, EN., Antonopoulou, S., et al.[2014]

The solid lipid nanoparticle (SLN) formulation of DHA-dFdC showed a high oral bioavailability of approximately 68%, significantly improving the delivery of this promising antitumor compound compared to traditional solutions.

In a mouse model with melanoma, the oral administration of DHA-dFdC-SLNs significantly increased survival rates compared to the standard DHA-dFdC solution, indicating enhanced therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of a Solid Lipid Nanoparticle Formulation on the Bioavailability of 4-(N)-Docosahexaenoyl 2', 2'-Difluorodeoxycytidine After Oral Administration. Valdes, SA., Alzhrani, RF., Lansakara-P, DSP., et al.[2021]

A series of N-acyl derivatives of 5-fluorouracil (5-FU) were developed, showing increased stability and hydrolysis rates under physiological conditions, which suggests improved efficacy as potential antitumor agents.

These derivatives can easily integrate into lipid bilayers and demonstrated significant cytostatic activity against human breast lymphoma cells, indicating their potential for use in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Synthesis and properties of 5-fluorouracil derivatives]. Semakov, AV., Blinkov, AA., Gaenko, GP., et al.[2019]

The study characterized the lipid composition of pulmonary surfactant in dogs, revealing that phosphatidylcholine (PC) makes up 75% of the surfactant, with 1,2-diacylPC being the major form (95%).

Platelet-activating factor-like activity was identified in the surfactant of some dogs, indicating potential biological activity, which was affected by chemical modifications, suggesting a complex role of these lipids in pulmonary function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Occurrence of glyceryl ethers in the phosphatidylcholine fraction of surfactant from dog lungs. Kumar, R., King, RJ., Hanahan, DJ.[2019]

Enriching cell membranes with polyunsaturated fatty acids, like docosahexaenoic acid, increases the sensitivity of cancer cells to the ether lipid drug BM 41.440, suggesting that membrane composition can enhance drug efficacy.

The increased cytotoxicity is not due to changes in drug transport or accumulation but may be linked to altered oxidative processes, highlighting the membrane as a key target for ether lipid action and offering new therapeutic strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Membrane lipid modification and sensitivity of leukemic cells to the thioether lipid analogue BM 41.440. Petersen, ES., Kelley, EE., Modest, EJ., et al.[2014]

In rodent models of acute necrotizing pancreatitis (ANP), treatment with oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OXPAPC) significantly improved survival rates and reduced pancreatic injury, as evidenced by lower serum levels of amylase and lactate dehydrogenase.

OXPAPC's protective effects were linked to its ability to inhibit inflammatory pathways, including down-regulation of key signaling proteins and reduced activity of transcription factors involved in inflammation, suggesting a potential therapeutic mechanism for managing ANP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The therapeutic effect of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine in rodents with acute necrotizing pancreatitis and its mechanism. Li, L., Wang, XP., Wu, K.[2016]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0273230018302745

Intravenous toxicity and toxicokinetics of an HDL mimetic ... Fx-5A has been shown to reduce the progression of atherosclerosis in rabbits and mice (Amar et al., 2010). Fx-5A also displays anti-inflammatory and antioxidant ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6893859/

Intravenous Toxicity and Toxicokinetics of an HDL Mimetic, ... Fx-5A peptide complex (Fx-5A), a High Density Lipoproteins (HDL) mimetic, has been shown to reduce atherosclerosis.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04216342?tab=history&a=58

Record History | ver. 58: 2020-03-25 | NCT04216342 Fx-5A was specifically designed to remove excess cellular cholesterol via the ABCA1 transporter, which is thought to be one of the main anti-atherogenic ...

4. withpower.com withpower.com/trial/phase-1-cardiovascular-diseases-9-2021-f4e6a

Fx-5A Safety and Tolerability in Healthy Volunteers This trial is testing a new drug called Fx-5A, which mimics a part of good cholesterol to help remove bad cholesterol and reduce inflammation.

5. mdpi.com mdpi.com/2073-4409/10/3/597

Apolipoprotein Mimetic Peptides: Potential New Therapies ... Similar to 4F, it has been shown to be effective in reducing atherosclerosis in animal models [26] and to have anti-inflammatory effects in other animal models ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04216342

Study Details | NCT04216342 | Safety, Tolerability, ... Assess the safety and tolerability of the Fx-5A peptide complex. A complete study is defined by the procedures described up to day 7 after Fx-5A infusion, the ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04216342/safety-tolerability-pharmacokinetics-and-pharmacodynamics-of-fx-5a-in-healthy-volunteers

Safety, Tolerability, Pharmacokinetics and ... The current research project is designed as a Phase 1A, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics ...